11/2/2017 Genetic variants and cancer - exploring dietary solutions - Cancer Tutor

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Genetic variants and cancer

exploring dietary solutions
Dr. Kevin Conners +
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Posted October 23, 2017 Read time: 3 mins Print 1

Cancer is a complex disease involving numerous changes in cell physiology including

the metabolic process on how it may be fed. It is defined as cells that are undergoing
rapid replication thereby needing a constant source of both energy and byproducts for
cell creation.

Looking for genetic variants (defects) of genes that are responsible for tumor
suppression as well as genes that may give a cancer cell more direct access to fuel
sources may be important steps to help understand the disease and limit growth. The
decreased expression of tumor suppressor genes, our genomic watchman involved in
sensing and stopping aberrant cell replication, is a part of the problem that may allow
cancer to manifest. A better understanding of these genes and learning ways to
manipulate their expression is key.

Cancer needs a fuel source or a supply line. All

cells make energy through glucose metabolism
but cancer seems to require greater amounts.
A process known as aerobic glycolysis or the
Warburg effect is a robust metabolic hallmark
Cancer, above all other of most tumors. [3] Normal cells make energy
diseases, has countless through a process taking glucose (sugar)
secondary causes. But, even through a metabolic chain called glycolysis
for cancer, there is only one that makes a chemical called pyruvate.
prime cause. Summarized in a Pyruvate then converts to another chemical in
few words, the prime cause of the mitochondria (powerhouse) of the cell to
cancer is the replacement of enter a process that produces a lot of energy,
the respiration of oxygen in the goal of glucose metabolism. Cancer cells
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11/2/2017 Genetic variants and cancer - exploring dietary solutions - Cancer Tutor

normal body cells by a are different. They can force pyruvate down a
fermentation of sugar. different pathway making high quantities of
Otto Warburg lactic acid in the cytoplasm (the belly) of the
cell. There, lactate ferments forming an acid
environment and more fuel for cell
replication; but it isnt a very efficient system.
So, why do cancer cells do this?

The belief has been that cancer cells may have damaged mitochondria that don't allow
pyruvate to enter to make energy the way normal cells do. However, recent studies have
shown that, though cancer cells need energy for replication, they also need other
components. [2] Much like a factory creating shoes might need the energy to run the
machines; it also needs leather, rubber, and laces. Since cancer cells gobble up glucose
through various pathways, their need for it goes beyond simple energy production. [3]

Glucose can enter other metabolic pathways to make other components (leather,
rubber, and laces). Ultimately, the Warburg Effect supports a metabolic environment
that allows for rapid biosynthesis of both energy and materials to support growth and
proliferation of new cells in cancer.

Although there is no specific gene mutation common to all cancers, nearly all cancers
express aerobic glycolysis (the Warburg Effect) as discussed above, regardless of their
tissue or cellular origin. Genes for glycolysis are over-expressed and genes that make
enzymes to convert pyruvate to acetyl co-A in the mitochondria, as well as those that
help get pyruvate into the mitochondria, maybe under-expressed. Therefore, it might
behoove us to look at such genes in cancer patients. [5]

Every metabolic process is under the control of genetic factors making enzymes to
initiate action. Since cancer may be fueled through excess lactic acid formed when
pyruvate fails to take its normal path, would those individuals with variants on the
genes responsible to move pyruvate normally into healthy energy production be more
susceptible to cancer? Would a patient with cancer be more apt to express defects on
genes that might lead to accelerating production of a fuel source preferred by cancer
cells? Could we, by assessing such variants in a patients genes help formulate a plan to
help cut-off necessary supply lines? These are the questions only time and trials may
answer but ones that I feel are worthy to explore.

Some of the genes in question are the HIF1A, PDH, LDH, KRAS, and PTEN genes. All
have been proven to play a part in an excess lactic acid production. [6] For instance, the
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11/2/2017 Genetic variants and cancer - exploring dietary solutions - Cancer Tutor

PDH gene, most directly responsible for converting pyruvate to acetyl co-A, may be
down-regulated with genetic variants expressed. Its function is directly hindered by
excess HIF-1A expression as well as exogenous sources of toxins suggesting other
environmental influences can also be involved. Those with PDH and HIF defects may be
more apt to create access lactic acid, a fuel source for cancer. Dietary considerations in
such individuals might be to restrict upstream nutrients that feed that pathway
namely glucose.

In summary, healthy cells take glucose through a process called glycolysis to make
pyruvate. This makes some energy necessary for cell function. Pyruvate, through
enzymes produced by specific genes (HIF & PDH), then convert to acetyl co-A to make
much more energy for normal cell health. If one has variants on the genes responsible
for such conversions, has variants on genes responsible to aid lactic acids ability to
enter the mitochondria inside the cell, or lacks supportive substrates necessary to
convert pyruvate to acetyl co-A regardless of gene expression, the cell makes excess
lactic acid, a known fuel for cancer. Increase fuel equals increased growth.

Our hope is that by better understanding specific metabolic pathways, the genes that
drive them, as well as cofactors influencing flow, we can better formulate both a
nutritional and dietary plan to help cancer patients. For more information on specific
genetic testing, contact Conners Clinic.

Article Information
1. Cancer is a preventable disease that requires major lifestyle changes. Anand P, Kunnumakkara AB,
Sundaram C, Harikumar KB, et al. Pharm Res 2008, 25:2097-2116
2. Cancer Undefeated. Bailar JC, Gornik HL; N Engl J Med 1997, 336:1569-1574
3. Buzzai, M., Bauer, D.E., Jones, R.G., Deberardinis, R.J., Hatzivassiliou, G., Elstrom, R.L., and Thompson, C.B.
Oncogene. 2005; 24: 41654173

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CANCER, CELL METABOLISM, GLUCOSE, WARBURG EFFECT

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